OBJECTIVE: To examine whether the cavum septi pellucidi (CSP) is larger in second and third trimester fetuses with chromosomal abnormalities than in euploid fetuses. METHODS: Retrospective study utilizing stored 2D images of second and third trimester fetuses between 18 and 40 week' gestation from the Department of prenatal medicine at University of Tuebingen/ Germany,from the Center for Prenatal Diagnosis and Genetics in Nuremberg/ Germany and from the ultrasound department of the Hospital Bad Canstatt, Stuttgart/ Germany. The width of the CSP was measured by placing the callipers on the inner portion of its lateral borders. Two operators measured the CSP width. Both were blinded to the fetal karyotype and to the measurements obtained by the other operator. The normal range in euploid fetuses was computed based on the BPD by applying univariate regression analysis. The CSP width in euploid and aneuploid fetuses was transformed into z-scores and compared using student's t-test. Univariate regression analysis was used to determine the dependency of the z-scores and the head biometry. RESULTS: The study population consisted of 267 euploid pregnancies and 81 with trisomy 21, 50 with trisomy 18 and 8 with trisomy 13. In the euploid group, mean CSP width was 4.5(range 1.8 - 7.4) mm. Regression analysis showed a significant dependency between the CSP width and the BPD (CSP width = 0.658 + 0.064 x BDP in mm, r=0.781, p<0.0001). The 95(th) centile increased from 3.2 to 7.1mm for a BPD of 40 to 100 mm. In the group of fetuses with trisomy 21, 18 and 13, mean CSP width was 5.7 (range 2.8 - 10.5) mm, 7.9 (range 3.5 - 12.8) mm and 5.8 (range 4.0 - 9.0) mm, respectively. In 42.0% of the fetuses with trisomy 21, the CSP width was above the 95(th) centile. In trisomy 18 and 13, the CSP width was above the 95(th) centile in 92.0% and 37.5% of the cases respectively. CONCLUSION: A large CSP width should trigger a detailed ultrasound examination to further assess the risk for chromosomal abnormalities.